Loss of the Par3 polarity protein promotes breast tumorigenesis and metastasis.

McCaffrey LM, Montalbano J, Mihai C, Macara IG
Cancer Cell. 2012 22 (5): 601-14

PMID: 23153534 · PMCID: PMC3500525 · DOI:10.1016/j.ccr.2012.10.003

Loss of epithelial organization is a hallmark of carcinomas, but whether polarity regulates tumor growth and metastasis is poorly understood. To address this issue, we depleted the Par3 polarity gene by RNAi in combination with oncogenic Notch or Ras(61L) expression in the murine mammary gland. Par3 silencing dramatically reduced tumor latency in both models and produced invasive and metastatic tumors that retained epithelial marker expression. Par3 depletion was associated with induction of MMP9, destruction of the extracellular matrix, and invasion, all mediated by atypical PKC-dependant JAK/Stat3 activation. Importantly, Par3 expression is significantly reduced in human breast cancers, which correlates with active aPKC and Stat3. These data identify Par3 as a regulator of signaling pathways relevant to invasive breast cancer.

Copyright © 2012 Elsevier Inc. All rights reserved.

MeSH Terms (20)

Animals Breast Neoplasms Cell Adhesion Molecules Cell Cycle Proteins Cell Polarity Cell Proliferation Cell Transformation, Neoplastic Female Gene Expression Regulation, Neoplastic Humans Mammary Neoplasms, Experimental Matrix Metalloproteinase 9 Membrane Proteins Mice Neoplasm Metastasis Phosphorylation Protein Kinase C Proto-Oncogene Proteins p21(ras) RNA Interference Tumor Cells, Cultured

Connections (1)

This publication is referenced by other Labnodes entities:

Links